Methods and systems for treatment of acute ischemic stroke

ABSTRACT

Described are methods and systems for transcervical access of the cerebral arterial vasculature and treatment of cerebral occlusions, including ischemic stroke. The methods and devices may include methods and devices which may provide aspiration and passive flow reversal, those which protect the cerebral penumbra during the procedure to minimize injury to brain, as well as distal catheters and devices to remove an occlusion. The methods and devices that provide passive flow reversal may also offer to the user a degree of flow control. Devices and methods which provide a way to securely close the access site in the carotid artery to avoid the potentially devastating consequences of a transcervical hematoma are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority of the following U.S. ProvisionalPatent Applications: (1) U.S. Provisional Patent Application Ser. No.61/515,736, filed on Aug. 5, 2011; (2) U.S. Provisional PatentApplication Ser. No. 61/543,019, filed on Oct. 4, 2011; (3) U.S.Provisional Patent Application Ser. No. 61/547,597, filed on Oct. 14,2011; (4) U.S. Provisional Patent Application Ser. No. 61/579,581, filedon Dec. 22, 2011. The disclosures of the Provisional Patent Applicationsare hereby incorporated by reference in their entirety.

BACKGROUND

The present disclosure relates generally to medical methods and devicesfor the treatment of acute ischemic stroke. More particularly, thepresent disclosure relates to methods and systems for transcervicalaccess of the cerebral arterial vasculature and treatment of cerebralocclusions.

Acute ischemic stroke is the sudden blockage of adequate blood flow to asection of the brain, usually caused by thrombus or other emboli lodgingor forming in one of the blood vessels supplying the brain. If thisblockage is not quickly resolved, the ischemia may lead to permanentneurologic deficit or death. The timeframe for effective treatment ofstroke is within 3 hours for intravenous (IV) thrombolytic therapy and 6hours for site-directed intra-arterial thrombolytic therapy orinterventional recanalization of a blocked cerebral artery. Reperfusingthe ischemic brain after this time period has no overall benefit to thepatient, and may in fact cause harm due to the increased risk ofintracranial hemorrhage from fibrinolytic use. Even within this timeperiod, there is strong evidence that the shorter the time periodbetween onset of symptoms and treatment, the better the results.Unfortunately, the ability to recognize symptoms, deliver patients tostroke treatment sites, and finally to treat these patients within thistimeframe is rare. Despite treatment advances, stroke remains the thirdleading cause of death in the United States.

Endovascular treatment of acute stroke is comprised of either theintra-arterial administration of thrombolytic drugs such as recombinanttissue plasminogen activator (rtPA), or mechanical removal of theblockage, or often a combination of the two. As mentioned above, theseinterventional treatments must occur within hours of the onset ofsymptoms. Both intra-arterial (IA) thrombolytic therapy andinterventional thrombectomy involve accessing the blocked cerebralartery. Like IV thrombolytic therapy, IA thrombolytic therapy has thelimitation in that it may take several hours of infusion to effectivelydissolve the clot.

Mechanical therapies have involved capturing and removing the clot,dissolving the clot, disrupting and suctioning the clot, and/or creatinga flow channel through the clot. One of the first mechanical devicesdeveloped for stroke treatment is the MERCI Retriever System (ConcentricMedical, Redwood City, Calif.). A balloon-tipped guide catheter is usedto access the internal carotid artery (ICA) from the femoral artery. Amicrocatheter is placed through the guide catheter and used to deliverthe coil-tipped retriever across the clot and is then pulled back todeploy the retriever around the clot. The microcatheter and retrieverare then pulled back, with the goal of pulling the clot, into theballoon guide catheter while the balloon is inflated and a syringe isconnected to the balloon guide catheter to aspirate the guide catheterduring clot retrieval. This device has had initially positive results ascompared to thrombolytic therapy alone.

Other thrombectomy devices utilize expandable cages, baskets, or snaresto capture and retrieve clot. A series of devices using active laser orultrasound energy to break up the clot have also been utilized. Otheractive energy devices have been used in conjunction with intra-arterialthrombolytic infusion to accelerate the dissolution of the thrombus.Many of these devices are used in conjunction with aspiration to aid inthe removal of the clot and reduce the risk of emboli. Frank suctioningof the clot has also been used with single-lumen catheters and syringesor aspiration pumps, with or without adjunct disruption of the clot.Devices which apply powered fluid vortices in combination with suctionhave been utilized to improve the efficacy of this method ofthrombectomy. Finally, balloons, stents and temporary stents have beenused to create a patent lumen through the clot when clot removal ordissolution was not possible. Temporary stents, sometimes referred to asstentrievers or revascularization devices, may also be utilized toremove or retrieve clot as well as restore flow to the vessel.

Some Exemplary Issues with Current Technology

Interventions in the cerebral vasculature often have special accesschallenges. Most neurointerventional procedures use a transfemoralaccess to the carotid or vertebral artery and thence to the targetcerebral artery. However, this access route is often tortuous and maycontain stenosis plaque material in the aortic arch and carotid andbrachiocephalic vessel origins, presenting a risk of emboliccomplications during the access portion of the procedure. In addition,the cerebral vessels are usually more delicate and prone to perforationthan coronary or other peripheral vasculature. In recent years,interventional devices such as wires, guide catheters, stents andballoon catheters, have all been scaled down and been made more flexibleto better perform in the neurovascular anatomy. However, manyneurointerventional procedures remain either more difficult orimpossible because of device access challenges. In the setting of acuteischemic stroke where “time is brain,” these extra difficulties have asignificant clinical impact.

Another challenge of neurointerventions is the risk of cerebral emboli.During the effort to remove or dissolve clot blockages in the cerebralartery, there is a significant risk of thrombus fragmentation creatingembolic particles which can migrate downstream and compromise cerebralperfusion, leading to neurologic events. In carotid artery stentingprocedures CAS, embolic protection devices and systems are commonly usedto reduce the risk of embolic material from entering the cerebralvasculature. The types of devices include intravascular filters, andreverse flow or static flow systems. Unfortunately, because of thedelicate anatomy and access challenges as well as the need for rapidintervention, these embolic protection systems are not used ininterventional treatment of acute ischemic stroke. Some of the currentmechanical clot retrieval procedures use aspiration as a means to reducethe risk of emboli and facilitate the removal of the clot. For example,the MERCI Retrieval System recommends attaching a large syringe to theguide catheter, and then blocking the proximal artery and aspirating theguide catheter during pull back of the clot into the guide. However,this step requires a second operator, may require an interruption ofaspiration if the syringe needs to be emptied and reattached, and doesnot control the rate or timing of aspiration. This control may beimportant in cases where there is some question of patient tolerance toreverse flow. Furthermore, there is no protection against embolic debrisduring the initial crossing of the clot with the microcatheter anddeployment of the retrieval device. Aspiration systems such as thePenumbra System utilize catheters which aspirate at the face of the clotwhile a separate component is used to mechanically break up the clot.This system is limited and in the level of aspiration possible withcurrent catheter designs, and in some cases by the ability to bringlarger catheters to the location of the clot.

One severe drawback to current acute stroke interventions is the amountof time required to restore blood perfusion to the brain, which can bebroken down to time required to access to the blocked cerebral artery,and time required to restore flow through the occlusion. Restoration offlow, either through thrombolytic therapy, mechanical thrombectomy, orother means, often takes hours during which time brain tissue isdeprived of adequate oxygen. During this period, there is a risk ofpermanent injury to the brain tissue. Means to shorten the proceduretime, and/or to provide oxygen to the brain tissue during the procedure,would reduce this risk.

SUMMARY

Disclosed are methods and devices that enable safe, rapid and relativelyshort and straight transcervical access to the cerebral arteries totreat acute ischemic stroke. The methods and devices include distalcatheters and devices to remove the occlusion. Methods and devices arealso included to provide aspiration and passive flow reversal for thepurpose of facilitating removal of the occlusion as well as minimizingdistal emboli. The system offers the user a degree of flow control so asto address the specific hemodynamic requirements of the cerebralvasculature. The disclosed methods and devices also include methods anddevices to protect the cerebral penumbra during the procedure tominimize injury to brain. In addition, the disclosed methods and devicesprovide a way to securely close the access site in the carotid artery toavoid the potentially devastating consequences of a transcervicalhematoma.

In one aspect, there is disclosed a system of devices for treating anocclusion in a cerebral artery of a patient, comprising: a transcervicalaccess sheath adapted to be introduced into a common carotid artery viaan opening directly in the artery, the opening being positioned abovethe patient's clavicle and below a bifurcation location where thepatient's common carotid artery bifurcates into an internal carotidartery and external carotid artery, wherein the transcervical accesssheath has an internal lumen; a distal catheter sized and shaped to beinserted axially through the internal lumen of the transcervical accesssheath such that the distal catheter can be inserted into a cerebralartery via the transcervical access sheath, wherein the distal catheterhas an internal lumen defined by an inner diameter; an elongated innermember sized and shaped to be inserted axially through the lumen of thetranscervical access sheath, wherein the inner member has an internallumen; and a guidewire configured to be inserted into the cerebralartery via internal lumen of the inner member; wherein the inner memberhas an outer diameter configured to form a smooth transition between theinner diameter of the distal catheter and the outer diameter of theguidewire.

In another aspect, there is disclosed a system of devices for treatingan occlusion in a cerebral artery of a patient, comprising: atranscervical access sheath adapted to be introduced into a commoncarotid artery via an opening directly in the artery, the opening beingpositioned above the patient's clavicle and below a bifurcation locationwhere the patient's common carotid artery bifurcates into an internalcarotid artery and external carotid artery, wherein the transcervicalaccess sheath has an internal lumen; and a distal catheter sized andshaped to be inserted axially through the internal lumen of thetranscervical access sheath such that the distal catheter can beinserted into a cerebral artery via the transcervical access sheath,wherein the distal catheter has a first internal lumen and a smaller,second internal lumen, wherein a distal-most portion of the secondinternal lumen is positioned inside an extension that protrudes distallypast a distal opening formed by the first lumen.

In another aspect, there is disclosed a system of devices for treatingan occlusion in a cerebral artery of a patient, comprising: atranscervical introducer sheath adapted to be introduced into a commoncarotid artery via an opening directly in the artery, the opening beingpositioned above the patient's clavicle and below a bifurcation locationwhere the patient's common carotid artery bifurcates into an internalcarotid artery and external carotid artery, wherein the transcervicalintroducer sheath has an internal lumen; a flow line connected to theintroducer sheath, wherein the flow line provides a pathway for blood toflow from the introducer sheath to a return site; a hemostasis valve ona proximal region of the introducer sheath that provides access to theinternal lumen of the introducer sheath while preventing blood loss; anda guide catheter sized and shaped to be inserted through the hemostasisvalve into the internal lumen of the introducer sheath such that theguide catheter can provide access to a cerebral artery via an internalof the guide catheter.

In another aspect, there is disclosed a method of treating an occlusionin a cerebral artery, comprising: forming an incision in common carotidartery; inserting a transcervical access sheath through the incisioninto the common carotid artery and deploying a distal end of the sheathin the common or internal carotid artery, wherein the access sheath hasan internal lumen; inserting a first distal catheter into the internallumen of the access sheath; positioning a distal end of the first distalcatheter in the cerebral artery adjacent the occlusion; aspiratingthrough the first distal catheter to capture the occlusion at the distalend of the first distal catheter; and retracting the distal end of thefirst distal catheter into the access sheath to pull the occlusion intothe access sheath.

Other features and advantages should be apparent from the followingdescription of various embodiments, which illustrate, by way of example,the principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary embodiment of a system of devices fortranscervical access and treatment of acute ischemic stroke showing aballoon-tipped arterial access device inserted directly into the carotidartery, a distal catheter, a thrombectomy device.

FIG. 2 illustrates an alternate embodiment wherein the arterial accessdevice is inserted into the carotid artery through a separate introducersheath.

FIG. 3 illustrates an embodiment in which the introducer sheath has anocclusion balloon and a connection to a flow line.

FIG. 4 illustrates an alternate embodiment of the arterial access devicewhich has two occlusion balloons and an opening between the twoballoons.

FIG. 5 illustrates an alternate embodiment of the arterial access devicewhich includes two telescoping sections.

FIG. 6 illustrates an embodiment of a balloon-tipped anchor device.

FIG. 7 illustrates an embodiment of a mechanically expandable-tippedanchor guide wire.

FIG. 8 illustrates an embodiment of a distal catheter with a taperedco-axial inner member.

FIG. 9 illustrates another embodiment of a distal catheter with atapered co-axial inner member.

FIG. 10 illustrates an embodiment of a combined arterial access deviceand distal catheter.

FIGS. 11 and 12 illustrate embodiments of distal catheters having secondlumens to maintain guide wire access.

FIG. 13 illustrates an embodiment of a distal catheter and arterialaccess device configured to be telescoping.

FIG. 14 illustrates an alternate embodiment of the system with theaddition of an occlusion device.

FIG. 15 illustrates an embodiment of the system with the addition of anaspiration source, filter and one-way check valve attached to thearterial access device.

FIG. 16 illustrates an embodiment of the system with the addition of anaspiration source, filter and one-way check valve attached to both thearterial access device and distal catheter.

FIG. 17 illustrates an embodiment of the system with the addition of asingle aspiration source, filter and one-way check valve attached toboth the arterial access device and distal catheter, and a valveconnecting the two devices to the aspiration source.

FIG. 18 illustrates an embodiment of the system with the addition of aflow controller attached to both the arterial access device and distalcatheter.

FIG. 19 illustrates an embodiment of an aspiration source.

FIG. 20 illustrates an alternate embodiment of an aspiration source.

FIG. 21 illustrates an embodiment of the system with the addition of aflow reverse circuit that includes a venous return site.

FIGS. 22-29 illustrate embodiments of thrombectomy devices.

FIG. 30 illustrates an embodiment of a dual-lumen microcatheter.

FIG. 31 illustrates an embodiment of a distal perfusion catheter.

FIG. 32 illustrates an alternate embodiment of a distal perfusioncatheter.

FIGS. 33-36 illustrate different embodiments of distal perfusioncatheters with an occlusion balloon.

FIG. 37 illustrates another embodiment of a distal perfusion catheter.

FIG. 38 illustrates an embodiment of the system with the addition of adistal balloon catheter configured to perfuse proximal to the balloon.

FIGS. 39A-39D illustrates steps in usage of a distal balloon catheterconfigured to perfuse distal and/or proximal to the balloon.

DETAILED DESCRIPTION

Described herein are methods and devices that enable safe, rapid andrelatively short and straight transcervical access to the carotidarteries and cerebral vasculature for the introduction of interventionaldevices for treating ischemic stroke. Transcervical access provides ashort length and non-tortuous pathway from the vascular access point tothe target cerebral vascular treatment site, thereby easing the time anddifficulty of the procedure, compared for example to a transfemoralapproach. Additionally, this access route reduces the risk of emboligeneration from navigation of diseased, angulated, or tortuous aorticarch or carotid artery anatomy.

FIG. 1 shows a system of devices for accessing the common carotid arteryCCA via a transcervical approach and for delivering devices to thecerebral vasculature. The system includes an arterial access device 2010(sometimes referred to as an arterial access sheath), such as a sheath,having an internal lumen and a port 2015. The arterial access device2010 is sized and shaped to be inserted into the common carotid arteryvia a transcervical incision or puncture and deployed into a positionthat provides access to the cerebral vasculature, for example the commonor internal carotid artery. The port 2015 provides access to thearterial access device's internal lumen, which is configured forintroducing additional devices into the cerebral vasculature via thearterial access device 2010.

In an embodiment, transcervical access to the common carotid arterydirectly with the arterial access device 2010 is achieved percutaneouslyvia an incision or puncture in the skin. In an alternate embodiment, thearterial access device 2010 accesses the common carotid artery CCA via adirect surgical cut down to the carotid artery. In another embodiment,the arterial access device provides access to the basilar artery BA orposterior cerebral arteries PCA via a cut down incision to in thevertebral artery or a percutaneous puncture of the vertebral artery foraccess to occlusions in the posterior cerebral vasculature such as theposterior cerebral artery or basilar artery. The arterial access devicemay include an occlusion balloon, to block antegrade flow. For entryinto the common carotid artery, the arterial access device is insertedinto an opening directly in the common carotid artery, the opening beingpositioned above the patient's clavicle and below a bifurcation locationwhere the patient's common carotid artery bifurcates into an internalcarotid artery and external carotid artery. For example, the opening maybe located at distance of around 5 cm to 7 cm below a bifurcationlocation where the patient's common carotid artery bifurcates into aninternal carotid artery and external carotid artery.

The system may also include one or more distal catheters 2030 to providedistal access and localized aspiration at a location distal of thedistal-most end of the arterial access device 2010. A single distalcatheter may be adequate for accessing and treating the occlusion orocclusions. A second, smaller diameter distal catheter may be insertedthrough the first catheter or exchanged for the first catheter if moredistal access is desired and not possible with the initial distalcatheter. In an embodiment, the distal catheter 2030 is configured to beinserted into the internal lumen of the arterial access device 2010 viathe port 2015. The distal catheter 2030 may use a previously placedguide wire, microcatheter, or other device acting as a guide rail andsupport means to facilitate placement near the site of the occlusion.The distal catheter may also utilize a dilator element to facilitateplacement through the vasculature over a guidewire. Once the distalcatheter is positioned at or near the target site, the dilator may beremoved. The distal catheter 2030 may then be used to apply aspirationto the occlusion. The catheter 2030 or dilator may also be used todeliver additional catheters and/or interventional devices to the siteof the occlusion.

The methods and devices also include devices for active aspiration aswell as passive retrograde flow to facilitate removal of the occlusionand/or minimize distal emboli. The system offers the user a degree ofblood flow control so as to address the specific hemodynamicrequirements of the cerebral vasculature. The system may include a flowcontroller, which allows the user to control the timing and mode ofaspiration from one or more of the devices.

With reference still to FIG. 1, a thrombectomy device 4100 such as astentriever or a coil retriever that has been configured fortranscervical access may be deployed through the arterial access deviceto the site of the thrombotic blockage. The thrombectomy device 4100 isinserted through the arterial access device 2010 and deployed across theocclusion in the cerebral vessel via a microcatheter. If desired, adistal catheter 2030 may be used to facilitate navigation of thethrombectomy device to the site of the occluded vessel, and/or toprovide aspiration at the site of the occlusion during retrieval of theclot by the thrombectomy device. The clot is retrieved by pulling backon the thrombectomy device and microcatheter in tandem into the distalcatheter 2030, if used, and thence into the arterial access device 2010.

The disclosed methods and devices also include devices to protect thecerebral penumbra during the procedure to minimize injury to the brain.A distal perfusion device may be used during the procedure to provideperfusion to the brain beyond the site of the occlusion, therebyreducing the injury to the brain from lack of blood. These perfusiondevices may also provide means to reduce the forward blood pressure onthe occlusion in the vessel and thus assist in removing the occlusionwith either aspiration, mechanical means, or both.

In addition, the disclosed methods and devices provide means to securelyclose the access site to the cerebral arteries to avoid the potentiallydevastating consequences of a transcervical hematoma. The presentdisclosure provides additional methods and devices.

Exemplary Embodiments Arterial Access Device

The arterial access device 2010 as shown in FIG. 1 is configured to bedirectly inserted into the common carotid artery CCA without use of aseparate introducer sheath. In this configuration, the entry or distaltip of the device is tapered and includes a tapered dilator so as toallow smooth introduction of the device over a guide wire into theartery. The device 2010 may include an occlusion balloon 2020 which isconfigured to occlude the artery when inflated. In an alternateembodiment, the arterial access device 2010 does not include anocclusion balloon. The arterial access device also includes a proximaladaptor. This proximal adaptor includes a proximal port 2015 with ahemostasis valve, to allow introduction of devices while preventing orminimizing blood loss during the procedure. In an embodiment, this valveis a static seal-type passive valve. In an alternate embodiment, thisvalve is an adjustable-opening valve such as a Tuohy-Borst or rotatinghemostasis valve (RHV). The hemostasis valve may be integral to theproximal adaptor, or may be attached separately to the proximal end ofthe adaptor via a Luer connection. The arterial access device 2010 mayalso include a connection to a flow line 2025 (or shunt) which may beconnected to means for passive or active reverse flow. The flow line2025 has an internal lumen that communicates with an internal lumen ofthe arterial access device 2010 for shunting blood from the arterialaccess device. In an embodiment, the flow line 2025 is a side arm orY-arm 2027 that is attached to and extends from the arterial accessdevice 2010 at a location between the distal and proximal ends of thearterial access device 2010. As shown in FIG. 1, the flow line 2025 islocated distal of the location where devices enter the proximal port2015 of the arterial access device. In an alternate embodiment, the flowline 2025 is attached to the Y-arm of a separately attached Tuohy Borstvalve.

The arterial access device 2010 may also include a lumen for ballooninflation. This lumen fluidly connects the balloon to a second Y-arm onthe proximal adaptor. This Y-arm is attached to a tubing 2028 whichterminates in a one-way stopcock 2029. An inflation device such as asyringe may be attached to the stopcock 2029 to inflate the balloon whenvascular occlusion is desired.

In an embodiment as shown in FIG. 2, the arterial access device is aguide catheter 2105 which is inserted through the proximal hemostasisvalve 2012 of a separate introducer sheath 2110 into the CCA. Thearterial access device also includes a proximal adaptor. This proximaladaptor includes a proximal port 2015 with a hemostasis valve, to allowintroduction of devices while preventing or minimizing blood loss duringthe procedure. The guide catheter 2105 may include a lumen for ballooninflation. This lumen is attached to a Y-arm in the proximal adaptor,which is connected to a tubing 2128. The tubing 2128 terminates in aone-way stopcock 2129 for connection to a balloon inflation device. Theguide catheter 2105 may include a second Y-arm 2107 that communicateswith a flow line 2125. Introduction through the separate sheath 2110allows removal of the guide catheter 2105 for flushing outside thepatient and reinserting, or for exchanging the guide catheter 2105 withanother guide catheter without removing the introducer sheath 2110, thusmaintaining access to the artery via the transcervical incision. Thisconfiguration also allows repositioning of the occlusion balloon 2020during the procedure without disturbing the arterial insertion site. Theembodiment of FIG. 2 also allows removal of the arterial access device2105 and then insertion of a vessel closure device through theintroducer sheath 2110 at the conclusion of the procedure.

In a variation of this embodiment, as shown in FIG. 3, the introducersheath 2110 includes an occlusion balloon 2205 and an inflation line andtubing 2318. The introducer sheath 2110 may also include a connection toa flow line 2310 for passive or active reverse flow, wherein passive oractive reverse flow may configured as described in U.S. patentapplication Ser. No. 12/176,250 and U.S. patent application Ser. No.12/834,869, which are incorporated herein by reference. This embodimentmay be useful if the patient had a carotid stenosis in addition to acerebral artery blockage, and the user wished to treat the carotidstenosis under static or reverse flow conditions as described in thereference patent application either prior or after treating the cerebralartery blockage.

In yet another embodiment, as shown in FIG. 4, the arterial accessdevice is a device 2105 a with two occlusion balloons 2405 and 2410 anda side opening 2415 positioned between the two balloons. The distalocclusion balloon 2410 is located at or near the distal end of thearterial access device 2105 a, and the proximal occlusion balloon 2405is located between the distal end and the proximal end of the workingportion of the arterial access device. The distal occlusion balloon 2410is sized and shaped to be placed in the external carotid artery ECA andthe proximal occlusion balloon 2405 is sized and shaped to be placed inthe common carotid artery CCA. Such a dual balloon configuration stopsflow into the internal carotid artery ICA from both the CCA and the ECA,which has an effect functionally the same as an occlusion balloonpositioned in the ICA without inserting a device into the ICA. This maybe advantageous if the ICA were diseased, whereby access may causeemboli to dislodge and create embolic complications, or the access tothe ICA were severely tortuous and difficult to achieve, or both. Theside opening 2415 in the working section of the arterial access device2105 permits a device 2416 to be introduced via the arterial accessdevice 2105 a and inserted into the ICA via the side opening 2415 whileflow is stopped or reversed, to reduce or eliminate the risk of distalemboli. This device 2416 may then be advanced to the location of thecerebral artery occlusion to treat the occlusion.

In yet another embodiment, as shown in FIG. 5 the arterial access deviceis a multi-part (such as two-part) telescoping system 2105 b. The firstpart is an introducer sheath 2110 b which is configured to be insertedtranscervically into the CCA. The second part is a distal extension 2110c which is inserted through the proximal end of the introducer sheath2110 b and which extends the reach of the sheath into the ICA. Thedistal end of the sheath 2110 b and the proximal end of the extension2110 c form a lap junction 2113 when the extension is fully inserted,such that there is a continuous lumen through the two devices. The lapjunction may be variable length, such that there is some variability inthe length of the combined telescoping system 2105 b. The distalextension 2110 c includes a tether 2111 which allows placement andretrieval of the distal extension 2110 c through the sheath 2110 b. Inan embodiment, the distal extension includes an occlusion balloon. Inthis embodiment the tether include a lumen for inflation of the balloon.This tether can be connected on the proximal end to a balloon inflationdevice. This configuration provides the advantages of the two-partsystem shown in FIG. 2, without compromising the luminal area.

In an embodiment, the working portion of the arterial access devicewhich enters the artery is constructed in two or more layers, includingfor example a first layer and a second layer. An inner liner isconstructed from a low friction polymer such as PTFE(polytetrafluoroethylene) or FEP (fluorinated ethylene propylene) toprovide a smooth surface for the advancement of devices through theinner lumen. An outer jacket material providing mechanical integrity tothe liner may be constructed from materials such as Pebax, polyethylene,nylon, or the like. A third layer may consist of a reinforcement betweenthe liner and the jacket. The purpose of the reinforcement layer is toprevent flattening or kinking of the inner lumen as the device navigatesthrough bends in the vasculature, and provide unimpeded means for deviceaccess as well as aspiration or reverse flow. The reinforcement may bemade from metal such as stainless steel, Nitinol, or the like, or stiffpolymer such as PEEK. The structure may be a coil or braid, or tubingwhich has been laser-cut or machine-cut so as to be flexible. Inaddition, the device may have a radiopaque marker at the distal tip tofacilitate placement of the device using fluoroscopy. In an embodiment,the working portion of the device may have a hydrophilic coating toimprove the ease of advancement of the device through the vasculature.

In an embodiment, the working length of the arterial access device is ofa length configured to occlude the proximal internal carotid artery wheninserted from the CCA, for example 10-15 cm. In an alternate embodiment,the working length of the arterial access device is of a length suitablefor closure with a vessel closure device, for example 11 cm or less. Inanother embodiment the device is of a length configured to occlude thedistal cervical internal carotid artery (ICA) when inserted from theCCA, for example 15-25 cm. In yet another embodiment, the arterialaccess device is of a length configured to occlude the petrous,cavernous, or terminal portion of the ICA when inserted from the CCA,for example 20-35 cm. In this embodiment, the distal-most portion (whichmay have a length of about 3 to about 6 cm) of the arterial accessdevice may be configured to be more flexible to accommodate thecurvature in the petreous portion of the ICA. This additionalflexibility may be achieved by using a lower durometer outer jacketmaterial in this section. Alternately, the wall thickness of the jacketmaterial may be reduced, and/or the density of the reinforcement layermay be varied to increase the flexibility. For example the pitch of thecoil or braid may be stretched out, or the cut pattern in the tubing maybe varied to be more flexible. The distal most portion of the arterialaccess device may also be tapered or stepped down to a smaller diameter.

The arterial access device as described above has a working length whichis considerably shorter than access devices which are placed from anaccess location in the femoral artery. The distance from the femoralartery to the CCA is about 60-80 cm, thus devices which utilize a CCAaccess site may be shorter by approximately this amount. Comparabledevices which are designed for femoral arterial access are typically80-95 cm in length for devices to be deployed in the cervical ICA (e.g.the Balloon Guide, Concentric, Inc.) or 95-105 cm in length designed toaccess the petrous ICA (e.g. the Neuron 6F Guide, Penumbra, Inc.) Theshorter lengths of access devices disclosed herein reduces theresistance to flow through the lumen of these devices and increases therate at which aspiration may occur. In an example embodiment, thearterial access device has a length of about 10 cm to about 40 cm. In anembodiment, the length of the arterial access device is about 10.5 cmand the guide catheter has a length of about 32 cm.

The arterial access device may also include a removable proximalextension to allow the user to insert devices into the proximal port ofthe proximal extension and from there into the lumen of the arterialaccess device while minimizing exposure of the user's hands toradiation. An example of a proximal extension design is described inco-pending U.S. patent application Ser. No. 12/540,341, filed Aug. 12,2009, which is incorporated herein by reference. U.S. patent applicationSer. No. 12/633,730, U.S. patent application Ser. No. 12/645,179, andU.S. patent application Ser. No. 12/966,948 are also incorporated byreference herein.

Distal Catheter Exemplary Embodiments

With reference again to FIG. 1, the distal catheter 2030 is configuredto be inserted through the arterial access device distal to the ICA andcerebral vessels, to a location as far as the thrombotic occlusion 10.The distal catheter 2030 has a length longer than the length of thearterial access device such that the distal catheter's distal end canprotrude from the distal opening of the arterial access device by about15-25 cm. The distal catheter is also more flexible than the arterialaccess device, due to the anatomy of the distal vasculature. A proximalport 2035 with a hemostasis valve may be situated on the proximal end ofdistal catheter 2030, to allow introduction of devices such as amicrocatheter, guide wire, or thrombectomy device while preventing orminimizing blood loss during the procedure. In an embodiment, this valveis an adjustable-opening valve such as a Tuohy-Borst or rotatinghemostasis valve (RHV). The hemostasis valve may be integral to thecatheter proximal adaptor, or may be attached separately to the proximalend of the catheter via a Luer connection.

As with the arterial access device, the distal catheter 2030 may also bemade with a two or more layer construction as described above. Thedistal catheter may be configured according to the description of theworking portion of the arterial access device described above. Inaddition, the distal catheter may have a radiopaque marker at the distaltip to facilitate placement of the device using fluoroscopy. In anembodiment, the working portion of the device may have a hydrophiliccoating to improve the ease of advancement of the device through thevasculature. In an embodiment, the distal-most portion is constructed tobe more flexible than the proximal portion, by means as described abovefor the arterial access device.

The distal catheter 2030 has a working length configured to reach theterminal ICA and cerebral vessels when placed through the arterialaccess device 2010. In an embodiment, the working length is 40 to 80 cm.A distal catheter with this length would allow a much higher rate ofaspiration than catheters designed for transfemoral access. For example,a distal catheter configured for transfemoral access to the cerebralcirculation has a length of 115 cm and an inner diameter of 0.057″ (theDAC 057 Catheter, Concentric Medical, Mountain View, Calif.) has a flowrate of 113 ml/min with fluid of 3.2 centipoise (cp, equivalent toblood) when connected to an aspiration pump set at a vacuum of 22 in Hg.A distal catheter 2030 configured for transcervical access into the CCAto the cerebral circulation (such as described herein) may have a lengthof 50 cm, with a similar inner diameter. As flow resistance is linearwith length of the tube according to Poiseuille's equation for flowthrough a tube, the catheter 2030 would have a flow rate of more thantwice the transfemoral catheter, specifically a flow rate of 260 ml/minwith 3.2 cp fluid when connected to an aspiration pump set at 22 in Hg,or, about 2.3 times the aspiration rate of a transfemoral system. Asimilar increase in aspiration rate would also be seen with manualsyringe aspiration or other aspiration source. In addition, because thetranscervical access site is much closer than the transfemoral site withmany less turns, there is less need for as high a degree of torquestrength in the walls of the catheter, thus a transcervically placedcatheter 2030 may be constructed with thinner wall construction, withequal or better ability to be placed in the target anatomy. A thinnerwall would result in large inner lumen, yielding even more advantage inflow rate. As the flow resistance is proportional to diameter to thefourth power, even small improvements in luminal area result in largeradvances in increased flow rate. In an embodiment, a distal catheter maybe sized to reach the terminal ICA only (and not the more distalcerebral arteries). In this embodiment, the distal catheter may have aninner diameter of 0.070″ to 0.095″ and a length of 25-50 cm. In anotherembodiment, the distal catheter may be sized to reach the more distalcerebral arteries, with an inner diameter of 0.035″ to 0.060″ and alength of 40-80 cm.

As with the arterial access device, the distal catheter may have avariable stiffness shaft. In this embodiment, the distal-most portion(which may have a length of about 3 to about 6 cm) of the distalcatheter may be configured to be more flexible to accommodate thecurvature in the cerebral vessels. This additional flexibility may beachieved by using a lower durometer outer jacket material in thissection. The shaft may have increasingly stiff sections towards the moreproximal section of the shaft, with the proximal most portion having thestiffest shaft section.

In an embodiment, an occlusion balloon 2040 may be disposed on thedistal catheter 2030 and can be used to occlude an artery such as tolimit forward arterial flow or pressure, which would improve theconditions that permit aspiration as well as removal of the occlusion.

With reference still to FIG. 1, the distal catheter 2030 may alsoinclude a proximal adaptor with a Y-arm for a flow line 2045 (or shunt).The flow line 2045 has an internal lumen that communicates with aninternal lumen of the distal catheter 2030. The proximal adaptor alsoincludes a proximal hemostasis valve 2035 for the insertion ofguidewires, microcatheters, or other catheters. In an embodiment, theproximal adaptor is permanently attached to the distal catheter 2030. Inanother embodiment, the proximal adaptor is a female Luer connector towhich a separate Tuohy-Borst valve with a Y-arm can be attached.

In another embodiment, a distal catheter system includes an anchordevice which is configured to be easily navigable through thevasculature to a location distal to the cerebral occlusion. When theanchor is deployed, it may be used as a rail and counter force tofacilitate advancement of the distal catheter to the proximal face ofthe occlusion. An example as shown in FIG. 6 is a microcatheter 2505with a distal balloon 2510. The microcatheter 2505 is placed over aguidewire 2515 through the occlusion 10 and then the distal balloon 2510is inflated. Alternately, the microcatheter has an atraumatic guidewiretip built in and is advanced as a stand-alone device. The distalcatheter 2030 can then use the shaft of the microcatheter 2505 as a railto be advanced towards the occlusion 10, as is done in conventionaltechniques. However, because the balloon 2510 is inflated, the distalend of the microcatheter 2505 is anchored against the clot and/or thevessel wall and provides counter force to the advancing distal catheter2030. Some of the force may be translated to the occlusion itself, andmay help remove the clot. The guidewire 2515 remains in place duringthis maneuver, such that if the anchor (i.e., the balloon 2510) anddistal catheter 2030 need to be re-advanced to attempt again to removethe occlusion 10, access is maintained across the occlusion with theguide wire 2515.

The atraumatic distal anchor can be a device other than a balloon. Forexample, other atraumatic distal anchors may include microcatheters withmechanically expandable-tips such as a braid, coil, or molly-boltconstruction. The expandable tip can be configured to be sufficientlysoft and to provide sufficient force along a length of the microcatheterso as to reduce focal pressure against the vessel wall and minimizevessel wall injury.

Another variation of this embodiment as shown in FIG. 7 is a guidewire2615 with an expandable tip 2620 such as a balloon or expandable cage orstent. The guidewire 2615 may be placed in the vasculature using amicrocatheter and then deployed when the microcatheter is retracted. Theexpandable portion of the guidewire 2615 device may be formed fromseparate braided filaments or cut from a single hypotube and expand witha counterforce actuating member. For example the proximal end of theexpandable tip may be attached to the distal end of a hollow hypotube,and the distal end attached to a wire which runs the length of thehypotype. When the wire is pulled back, the expandable tip is shortenedin length and expanded in diameter. Pushing the wire forward wouldcollapse the expandable tip.

A cause of difficulty in advancing larger size catheters is the mismatchbetween the catheter and the inner components. One technique foradvancing the larger size catheters is called a tri-axial technique inwhich a smaller catheter, either a microcatheter or a smaller distalcatheter, is placed between the large catheter and the guide wire.However, with current systems the smaller catheter has a diametermismatch between either the larger catheter, the guide wire, or both,which creates a step in the system's leading edge as the system isadvanced in the vasculature. This step may cause difficulty whennavigating very curved vessels, especially at a location where there isa side-branch, for example the ophthalmic artery. In an embodiment, asshown in FIG. 8, the distal catheter 2030 is supplied with a taperedco-axial inner member 2652 that replaces the smaller catheter generallyused. The inner member 2652 is sized and shaped to be inserted throughthe internal lumen of the distal catheter. The inner member 2652 has atapered region with an outer diameter that forms a smooth transitionbetween the inner diameter of the distal catheter 203 and the outerdiameter of a guidewire 2515 or microcatheter that extends through aninternal lumen of the inner member 2652. In an embodiment, the tapereddilator or inner member 2652, when positioned within the distalcatheter, creates a smooth transition between the distal-most tip of thelarger distal catheter 2030 and the outer diameter of a guide wire 2515which may be in the range of 0.014″ and 0.018″ diameter for example. Forexample, the inner luminal diameter may be between 0.020″ and 0.024″. Inanother embodiment, the inner diameter is configured to accept amicrocatheter with an outer diameter in the range of 0.030″ to 0.040″ oran 0.035″ guide wire in the inner lumen, for example the inner luminaldiameter may be 0.042″ to 0.044″.

In a variation of this embodiment, shown in FIG. 9, in addition to thetapered region, the inner member 2652 includes an extension formed of auniform diameter or a single diameter, distal-most region 2653 thatextends distally past the tapered portion of the inner member 2652. Inthis embodiment the distal region 2653 of the inner member 2652 mayperform some or all of the functions that a microcatheter would doduring a stroke interventional procedure, for example cross theocclusion to perform distal angiograms, inject intraarterialthrombolytic agents into the clot, or deliver mechanical thrombectomydevices such as coil retrievers or stent retrievers. In this manner, amicrocatheter would not need to be exchanged for the dilator for thesesteps to occur.

The material of the dilator (inner member 2652) is flexible enough andthe taper is long enough to create a smooth transition between theflexibility of the guide wire and the distal catheter. Thisconfiguration will facilitate advancement of the distal catheter throughthe curved anatomy and into the target cerebral vasculature. In anembodiment, the dilator is constructed to have variable stiffness, forexample the distal most section is made from softer material, withincreasingly harder materials towards the more proximal sections.

In an embodiment, distal end of the tapered dilator has a radiopaquemarker such as a platinum/iridium band, a tungsten, platinum, ortantalum-impregnated polymer, or other radiopaque marker. In anembodiment, the tapered dilator is constructed with variable stiffness.For example, the distal segment of the dilator may be constructed with asofter material, with successively stiffer materials towards theproximal end. As shown in FIG. 1, the distal catheter 2030 can be itsown catheter that is separate and removable from the arterial accessdevice. In another embodiment, shown in FIG. 10, the distal catheter andthe arterial access device are combined to be a single device 2710 witha continuous lumen extending through the length of the device. Aproximal portion 2720 comprises the arterial access sheath and a distalportion 2730 functions as the distal catheter. An occlusion balloon 2715is located between the distal and proximal portion. The distal portion2730 is constructed to be more suited for navigating the cerebralvasculature. In particular, the distal portion 2730 is more flexible andtapered to a smaller diameter than the proximal portion 2720.

In another embodiment, as shown in FIGS. 11 and 12, the distal catheterhas a second lumen to maintain guide wire access to facilitatere-advancement or exchange of the distal catheter without recrossing thetarget anatomy. In an embodiment, shown in FIG. 11, the distal catheterhas two lumens which terminate together at the distal tip: a main lumenand a second guidewire lumen. The termination may be such that adistal-facing surface is arranged at an angle (relative to thelongitudinal axis of the catheter), to facilitate tracking of thecatheter through the vasculature. In another embodiment, shown in FIG.12, the second guidewire lumen is inside an extension 1247 that extendsout past the termination of the main lumen. The extension 1247 is adistal-most region of the distal catheter that protrudes distally pastan opening formed by the main lumen. The extension 1247 forms a shafthaving a reduced outer diameter relative to the outer diameter of thedistal catheter around the main lumen. The second lumen is smaller thanthe shaft of the main distal catheter, and may be positioned in oracross an occlusion while the distal end of the main lumen is positionedon the proximal face of an occlusion. The distal end of the main lumenmay be terminated at an angle as well, to facilitate tracking of thedevice.

In yet another embodiment, the distal catheter has an expandable tipportion. The expandable tip facilitates aspiration of an occlusion whenan aspiration device is connected to the proximal portion of the distalcatheter. The expandable tip portion may be constructed with amechanical structure such as a braid or stent structure, which can openor close in a repeatable manner. The mechanism for opening the tip maybe a pull-wire which shortens the expandable portion, or an outerretention sleeve which maintains the distal section in a small diameterbut when retracted allows the distal tip to expand. The distal sectionmay be covered with a membrane such that when aspiration is applied,either with the tip expanded or not, a vacuum may be applied at the verytip of the catheter. The expandable tip allows the catheter to maintaina small profile during tracking of the catheter to the target anatomy,but then expands the distal luminal area for facilitated capture ofocclusive material such as thrombus. The thrombus, once captured intothe distal catheter, may be sucked all the way into the aspirationdevice, or alternately will be lodged in the lumen of the distalcatheter where the catheter is no longer expanded, and at that point canbe removed by retraction of the entire distal catheter.

In another embodiment, shown in FIG. 13, the distal catheter 2830 is atelescopic attachment to the distal portion of the arterial accessdevice 2820. The distal region of the arterial access device 2820 hasone or more structures that telescopically extend in the distaldirection along the longitudinal axis of the arterial access device. Thestructures may also be telescopically collapsed such that they do notextend past the distal end of the arterial access device. When thestructures are telescopically expanded past the distal end of thearterial access device, the structures collectively form a continuousinner lumen. A tether element such as a wire 2835 may be connected tothe distal portion 2830 and extends out the proximal end of arterialaccess device such that the telescoping actuation may be accomplishedfrom the proximal end of the arterial access device. An expandablemember, such as balloon 2815, may be positioned on the device 2820.

FIG. 14 shows an alternate embodiment of the system wherein a secondarydevice, such as a balloon catheter 2502, is advanced through thearterial access device 2010 and into a collateral cerebral artery suchas the anterior cerebral artery ACA. The balloon catheter 2502 includesan expandable balloon 2530 that can be expanded in the collateralcerebral artery to occlude that artery. Occlusion of the collateralcerebral artery enhances suction and reverse flow through the cerebralvasculature, as described in detail below.

Exemplary Embodiments of Aspiration and Flow Control

Either or both the arterial access device 2010 and the distal catheter2030 may be connected to sources of passive or active aspiration viaflow lines 2025 or 2045 (FIG. 1) on the devices. The mode of aspirationmay be different for each device.

In FIG. 15, the flow line 2025 of the arterial access device 2010 isconnected to a delivery location, such as a receptacle 3100. A source ofaspiration 3125 may be coupled to the flow line 2025. The receptacle3100 and source of aspiration 3125 may be separate or may be combinedinto a single device such as a syringe. A filter 3418 and/or a checkvalve 3419 may be coupled with flow line 2025. In FIG. 16, the flow line2045 of the distal catheter 2030 is additionally or alternatelyconnected to a separate aspiration source 3425 and delivery location,such as receptacle 3105. The aspiration source 3425 and deliverylocation may be combined into a single device such as a syringe. Afilter 3418 and/or a check valve 3419 may coupled with the flow line2045.

FIG. 17 shows a system whereby both the arterial access device 2010 anddistal catheter 2030 are connected to the same aspiration source 3430via flow lines 2025 and 2045, respectively. A valve 3325 controls whichdevice is connected to the aspiration source 3430. The valve may enableone device, the other device, both devices, or neither device to beconnected to the aspiration source at any given time. The valve may be a3-way or 4-way stopcock. Alternately, the valve may be a flow controllerwith a simple actuation which selects the configuration as describedabove.

In an embodiment, a flow controller may facilitate control of multiplemeans of aspiration through multiple devices in a single unit. Thisconfiguration may facilitate use of the system by a single operator. Theflow controller may include one or more control interfaces that a usermay actuate to regulate which device is being aspirated, for example thearterial access device, the distal catheter, both, or neither. FIG. 18shows an embodiment of a system that utilizes such a flow controller3400. The flow controller 3400 is connected to the flow line 2025 of thearterial access device 2010 as well as to the flow line 2045 of thedistal catheter 2030. In this manner, the flow lines 2025 and 2045permit fluid to flow from the arterial access device 2010 and thecatheter 2030, respectively, to the flow controller 3400. The controller3400 may be connected to either or both a passive source of aspiration3410 and an active source of aspiration 3420. The flow controllerhousing 3429 contains control mechanisms to determine how and when eachdevice is connected to each source of aspiration. The control mechanismsmay also control the level of aspiration from each source. In addition,the controller may include a control that permits a pulsatile aspirationmode which may facilitate the breaking up and aspiration of the cerebralocclusion. The flow controller may have an interface for switchingbetween continuous and pulsatile aspiration modes. The controlmechanisms may be designed to be operable using one hand. For example,the control mechanisms may be toggle switches, push button switches,slider buttons, or the like. In an embodiment, the flow controller 3400has an interface that can enable the user to restore immediate antegradeflow to the cerebral circulation, for example with a single button orswitch that simultaneously deflates the occlusion balloon on thearterial access device and stops aspiration.

The active source of aspiration may be an aspiration pump, a regular orlocking syringe, a hand-held aspirator, hospital suction, or the like.In one embodiment, a locking syringe (for example a VacLok Syringe) isattached to the flow controller and the plunger is pulled back into alocked position by the user while the connection to the flow line isclosed prior to the thrombectomy step of the procedure. During theprocedure when the tip of the aspiration device (either the arterialaccess device or the distal catheter) is near or at the face of theocclusion, the user may open the connection to the aspiration syringe.This would enable the maximum level of aspiration in a rapid fashionwith one user, something that is currently not possible with existingtechnologies. In another embodiment, the aspiration source is ahand-held aspirator which is configured to be able to aspirate andrefill without disconnecting the aspiration device. In an example ofthis embodiment, the hand-held aspirator contains a chamber with aplunger that is moved up and down with a single-handed actuator. Thechamber includes input and output valves, such that when the plunger ismoved up and down there is a continuous source of aspiration into andout of the chamber without the need to remove and empty the chamber aswould be needed with a syringe. The chamber input is connected to thecatheter, and the chamber output is connected to a collection receptaclesuch as blood-collection bag. In an embodiment, this aspiration sourceis configured to be used with one hand only.

One disadvantage of current sources of aspiration is that the aspiratedblood is received into an external reservoir or syringe. This blood isgenerally discarded at the end of the procedure, and as such representsblood loss from the patient. In addition, pumps such as centrifugal orperistaltic pumps are known to cause damage to blood cells. Although itis possible to return blood from the external reservoir to the patient,the blood has been exposed to air or has been static for a period oftime, and there is risk of thrombus formation or damage to the bloodcells. Usually, aspirated blood is not returned to the patient to avoidrisk of thromboembolism.

FIG. 19 shows a cross-sectional view of an exemplary aspiration pumpdevice 3250 which is configured not to harm blood cells and which may beconfigured to return blood to the central venous system in real timeduring the procedure, so there is no reservoir in which the bloodremains static. The pump 3250 may be connected to either or both thearterial access device 2010 and distal catheter 2030. The pump device3250 includes a housing 3215 that encloses a chamber 3220 in which iscontained a portion of the flow line 2025. An expandable portion 3210 ofthe flow line 2025 contained within the chamber 3220 is formed of anelastic material that is at a reduced diameter in its natural state(shown in phantom lines in FIG. 19) but may be configured to change toan expanded diameter (shown in solid lines in FIG. 19). One or moreseals 3125, such as O-rings, seal the interface between the chamber 3220and the flow line 2025. A vacuum source 3230 is coupled to the chamber3220 and is configured to be operated to vary the pressure within thechamber 3220. Two one-way check valves 3235 are located in the flow line2025 on either side of the expandable portion 3210.

In operation of the pump device 3250, the vacuum source 3230 is operatedto create a reduced pressure within the chamber 3220 relative to thepressure within the flow line lumen 3210. The pressure differentialbetween the chamber 3220 and the flow line lumen 3210 causes theexpandable portion 3210 of the flow line 2025 to expand to an increasedvolume within the chamber 3220, as shown in solid lines in FIG. 32. Thisexpansion causes blood to be pulled into the expandable portion 3210from the sheath side of the flow line, shown by the “in” arrow, ascontrolled by the check valves 3235. The vacuum source 3230 may then beturned off so as to normalize the pressure within the chamber 3220. Thiscauses the expandable portion 3210 to revert to its smaller, naturaldiameter, as shown in phantom lines in FIG. 19. The check valves 3235causes the blood within the previously-expanded region of the flow line2025 to be expelled towards location 3120, as shown by the “out” arrowin FIG. 19. The vacuum source 3230 may be operated so as to oscillatethe expandable portion 3210 between the expanded and retracted state andtogether with the one-way check valves 3235 thereby drive fluid throughthe flow line lumen 3210.

FIG. 20 shows a pump system 3305 that includes a pair of pump device3205 a and 3205 b, each of which is of the type shown in FIG. 32. Thatis, each device 3205 includes a housing 3215 that contains a chamber inwhich a portion of the flow line 2025 is contained. The pump devices3205 a and 3205 b are connected in parallel to the flow line 2025 suchthat each pump device 3205 has a flow line 2025 with an expandableportion 3210. The pair of pump devices 3205 a and 3205 b may bealternated between expanded and retracted states to create a relativelycontinuous flow state through the pump system 3305. For example, thepump device 3205 a may be in the expanded state while the pump 3205 bmay be in the retracted state such that the pumps 3205 a and 3205 b arecollectively driving fluid through the pump system 3305 withoutinterruption.

A further advantage pump system 3250 or 3305 is that it may be used inconjunction with a passive reverse flow system which is configured toreturn blood to the central venous system, as is disclosed elsewhere inthis document. These two systems may share a venous return line, and areconnected by a valve or other flow control device.

The passive source of aspiration may be a site with lower pressure, forexample a sheath inserted into a central vein (for venous return) or anIV bag placed at a vertical level that would vary depending on whatamount of negative pressure is desired. FIG. 21 shows an exemplaryembodiment of a system 3500 that uses venous return to establish passiveretrograde flow into the arterial access device. The system 3500includes the arterial access device 3510, a venous return device 3515,and a flow line 3520 that provides a passageway for retrograde flow fromthe arterial access device 3510 to the venous return device 3515. A flowcontrol assembly 3525 interacts with the flow line 3520. The flowcontrol assembly 3525 is adapted to regulate and/or monitor theretrograde flow through the flow line 3520. The flow control assembly3525 interacts with the flow pathway through the flow line 3520 todetermine the state and level of flow through the flow line.

In an embodiment, the arterial access device 3510 at least partiallyinserts into the common carotid artery CCA and the venous return device3515 at least partially inserts into a venous return site, such as thefemoral vein or internal jugular vein, as described in more detailbelow. The venous return device 3515 can be inserted into the femoralvein FV via a percutaneous puncture in the groin. The arterial accessdevice 3510 and the venous return device 3515 couple to opposite ends ofthe flow line 3520 at connectors. The distal end of the arterial accessdevice 3510 with the occlusion element 3529 may be positioned in theICA. Alternately, in some circumstances where the ICA access isextremely tortuous, it may be preferable to position the occlusionelement more proximally in the common carotid artery. When flow throughthe internal carotid artery is blocked (using the occlusion element3529), the natural pressure gradient between the internal carotid arteryand the venous system causes blood to flow in a retrograde or reversedirection from the cerebral vasculature through the internal carotidartery and through the flow line 3520 into the venous system.

In another embodiment, the arterial access device 3510 accesses thecommon carotid artery CCA via a transcervical approach while the venousreturn device 3515 access a venous return site other than the femoralvein, such as the internal jugular vein. In another embodiment, thesystem provides retrograde flow from the carotid artery to an externalreceptacle, for example an IV bag, rather than to a venous return site.The arterial access device 3510 connects to the receptacle via the flowline 3520, which communicates with the flow control assembly 3525. Theretrograde flow of blood is collected in the receptacle. If desired, theblood could be filtered and subsequently returned to the patient. Thepressure of the receptacle could be set at zero pressure (atmosphericpressure) or even lower, causing the blood to flow in a reversedirection from the cerebral vasculature to the receptacle.

Exemplary Embodiments of Thrombectomy Devices

An exemplary embodiment of a thrombectomy device for use with any of thedisclosed systems of devices is a device such as those described abovebut that are configured for transcervical placement. Specifically, thethrombectomy device has a working length which would allow it to extendout of the arterial access device 2010 or distal catheter 2030 withenough length to access and cross the cerebral occlusion. Morespecifically, a thrombectomy device with a working length of between 80and 120 cm.

In an embodiment, a microcatheter which has been configured fortranscervical access is included as part of system 100. Morespecifically, a microcatheter with a working length of between 100 and140 cm is included in system 100. The microcatheter may be used forangiograms and/or delivery of thrombectomy devices.

Additional embodiments of thrombectomy devices are now described. FIG.22 shows an enlarged, side view of a distal region of an exemplarythrombectomy device 4100 that is formed of a self-expandable member 4112attached to an elongate flexible catheter 4115 that extends proximallyfrom the expandable member 4112. The expandable member 4112 is formed ofa plurality of longitudinal, intertwined or undulating struts that arearranged to form a plurality of cell structures that may bediamond-shaped. In an embodiment, the struts are coupled to a source ofenergy that permits sonic energy to be applied to the struts. Theexpandable member 4112 is configured to transition between a reducedsize and an enlarged size wherein the expandable member 4112 expandsradially outward from a first diameter to a second, greater diameterrelative to the longitudinal axis of the catheter 4115. The expandablemember 4112 may be formed for example from a single tube which has beenlaser cut in a geometry to create the struts, in a similar manner thatmany intravascular stents are manufactured. In an embodiment, theexpandable member 4112 is made of shape memory material, such asNitinol. The expandable member 4112 may be configured according toexpandable members described in U.S. Patent Publication No. 20110009875,which is incorporated herein by reference in its entirety.

In use, the expandable member 4112 is advanced through the vascularanatomy via the arterial access device described above. The expandablemember 4112 is positioned at the site of the thrombus while in theunexpanded state. The expandable member is then positioned within thelocation of the thrombus and caused to transition to its expanded state.In an embodiment, once the expandable member 4112 is expanded at thelocation of the thrombus, the expandable member is maintained in thatlocation for a period of time in order to create a perfusion channelthrough the thrombus that causes the thrombus to be lysed by theresultant blood flow passing through the thrombus. In such anembodiment, it is possible but not necessary that the expandable member4112 capture a portion of the thrombus for retrieval outside thepatient. When a sufficient portion of the thrombus has been lysed tocreate a desired flow channel through the obstruction, or outrightremoval of the obstruction is achieved by the resultant blood flow, theexpandable member 4112 may be withdrawn into the sheath 4100 andsubsequently removed from the patient. The expandable portion maycapture some or all of the thrombus while being withdrawn into thesheath.

In an embodiment, also shown in FIG. 22, an elongated perfusion catheter4120 is positioned longitudinally through the expandable member 4112.The perfusion catheter 4120 has a plurality of perfusion holes thatcommunicate with an internal lumen and a source of perfusion fluid. Theperfusion catheter 4120 is configured to perfuse fluid outwardly throughperfusion holes 4125. The perfusion holes may be used to perfusethrombolytic agents such as urokinase or tPA to aid in the dissolutionof the clot. Alternately, the perfusion holes may be used to perfuseneuroprotective agents and/or oxygenated blood.

FIG. 23 shows another embodiment wherein an elongated mechanical member4205 is positioned longitudinally through the expandable member 4112.The mechanical member 4205 generally extends along the longitudinal axisof the expandable member 4112. The mechanical member is configured toexert mechanical energy onto the thrombus when the expandable member4112 is positioned within the thrombus. The mechanical member 4205 maybe any of a variety of mechanical members, such as a corkscrew wire or abrush. The mechanical member can be moved to exert the mechanicalenergy, such as by rotating or vibrating the mechanical member 4205. Theembodiments of FIGS. 16 and 17 may be combined to provide perfusion andaspiration capabilities along with mechanical disruption capabilities.

Various other features may be used with or coupled to the expandablemember 4112. FIG. 24 shows an embodiment wherein a distal filter 4305 ispositioned at or near the distal end of the expandable member 4112. Thefilter 4305 is configured to capture emboli which may be generatedduring removal of the thrombotic obstruction, either through naturallysis of the thrombus or mechanical retrieval of the thrombus. In theembodiment of FIG. 25, a parachute-shaped member 4405 is positioned ator near the distal end of the expandable member 4112. The embodiment ofFIG. 19 includes a plurality of longitudinal struts 4605 that extendfrom a proximal end toward a distal end of the expandable member 4112,and are attached to parachute-shaped member 4405. The struts 4605 areconfigured to be pressed through the thrombus when deployed within thethrombus. When pressed through the thrombus, the struts 4605 pull theparachute-shaped member 4405 around the thrombus to capture it, and thedevice 4100 can then be withdrawn to pull the thrombus out of theartery.

In the embodiment of FIG. 26 an expandable dilatation member 4505, forexample a dilatation balloon is positioned within the expandable member4112. The dilation member 4505 may be expanded to dilate the thromboticocclusion and press the expandable member 4112. Once the dilation memberis deflated, the expandable member which is now engaged with the clotmay be pulled back to remove the thrombus out of the artery.

FIG. 27 shows another embodiment of a thrombectomy device comprised ofan elongated element 4705 positioned at a distal end of a distalcatheter 4710. The elongated element 4705 has an irregular shape alongits longitudinal axis, such as a corkscrew or undulating shape.Alternately, the elongated element is slidably positioned inside distalcatheter 4710. The elongated element 4705 may be made from springmaterial such as stainless steel or Nitinol, so that it may be retractedinto distal catheter 4710 when crossing the clot. After crossing, thecatheter 4710 is pulled back to expose the elongated element 4705 andallow it to take its irregular shape. The elongated element may bepositioned at the site of the thrombus and then manipulated, such as byshaking, rotating, waving, spinning, or moving back and forth, so as toexert mechanical energy onto the thrombus to break up the thrombus. Thedistal catheter 4710 is connected to an aspiration source to aspiratethe thrombus as it is being mechanically disrupted by elongated element4705.

In the embodiment of FIG. 28, an elongated catheter 4805 is sized andshaped to be positioned within the thrombus. The catheter 4805 includesperfusion holes 4810 that can be used to spray a perfusion fluid ontothe thrombus with sufficient force onto the thrombus to disrupt thethrombus. The elongated catheter 4805 may be delivered through anotherdistal catheter 4820. The distal catheter 4820 may be connected to anaspiration source to aspirate the thrombus as it is being fluidlydisrupted by the perfusion fluid from elongated catheter 4805. Thedistal end of the catheter 4805 may include an expandable occlusionelement 4815 to prevent perfusion fluid or disrupted thrombus fromtraveling downstream.

In another embodiment, shown in FIG. 29, a catheter 4900 includes duallumens that run in parallel along the length of the catheter 4900. Thedual lumens include an access lumen 4920 for deployment of anintervention device such as a thrombectomy device or a stentriever, aswell as a perfusion lumen 4930 for transmission of perfusion fluid,thrombolytic agent, or for aspiration of thrombus material.

It should be appreciated that other mechanical thrombectomy cathetersmay be used in a similar manner with the vascular access and reverseflow system as described above. Mechanical thrombectomy devices mayinclude variations on the thrombus retrieval device described earlier,such as coil-tipped retrievers, stent retrievers, expandable cages, wireor filament loops, graspers, brushes, or the like. These clot retrieversmay include aspiration lumens to lower the risk of embolic debrisleading to ischemic complications. Alternately, thrombectomy devices mayinclude clot disruption elements such as fluid vortices, ultrasound orlaser energy elements, balloons, or the like, coupled with flushing andaspiration to remove the thrombus. Some exemplary devices and methodsare described in the following U.S. Patents and Patent Publications,which are all incorporated by reference in their entirety: U.S. Pat.Nos. 6,663,650, 6,730,104; 6,428,531, 6,379,325, 6,481,439, 6,929,632,5,938,645, 6,824,545, 6,679,893, 6,685,722, 6,436,087, 5,794,629, U.S.Patent Pub. No. 20080177245, U.S. Patent Pub. No. 20090299393, U.S.Patent Pub. No. 20040133232, U.S. Patent Pub. No. 20020183783, U.S.Patent Pub. No. 20070198028, U.S. Patent Pub. No. 20060058836, U.S.Patent Pub. No. 20060058837, U.S. Patent Pub. No. 20060058838, U.S.Patent Pub. No. 20060058838, U.S. Patent Pub. No. 20030212384, and U.S.Patent Pub. No. 20020133111.

A major drawback to current thrombectomy devices is the need to re-crossthe occlusion with a guidewire and microcatheter if the thrombectomydevice did not remove enough of the occlusion to restore adequate flow,and additional attempts are needed to remove the occlusion. Currently, asingle-lumen microcatheter is used to deliver the thrombectomy device.The microcatheter is placed over a guidewire, the guidewire is thenremoved and the thrombectomy device is delivered. When removing theocclusion both the microcatheter and device are pulled back and theaccess across the occlusion is lost. Thus if the attempt at removal wasunsuccessful or incomplete and an additional attempt is required, theguidewire and microcatheter must again cross the occlusion. As mentionedabove, this extra step of re-crossing the occlusion takes time andincurs risk of distal vessel injury. An embodiment of this disclosure,shown in FIG. 30, is a microcatheter 4200 which includes at least twolumens, one lumen for a guide wire 2515 and the second to deliver athrombectomy device 4100 such as a stentriever or coil retriever. Thepresence of a second lumen for the guide wire may add outer profile to amicrocatheter over a microcatheter with just a single lumen. However,the reduced time and risk that may be provided by a second guidewirelumen can be advantageous. In addition, for use transcervically, theguidewire and/or the catheter walls may be scaled down to be less thanconventional wall thicknesses, to lower the overall increase needed toadd the extra lumen.

Exemplary Embodiments of Perfusion Devices

In an embodiment, the system may include a means to perfuse the cerebralvasculature distal to the thrombotic blockage and ischemic brain tissuevia a perfusion catheter delivered, for example, through the arterialaccess device 2010 to a site distal to the thrombotic occlusion 10. Theperfusion catheter is adapted to deliver a perfusion solution to adesired location. Perfusion solution may include, for example,autologous arterial blood, either from the flow line of a passivereverse flow circuit 3500 or from another artery, oxygenated solution,or other neuroprotective agent. In addition, the perfusion solution maybe hypothermic to cool the brain tissue, another strategy which has beenshown to minimize brain injury during periods of ischemia. The perfusioncatheter may also be used to deliver a bolus of an intra-arterialthrombolytic agent pursuant to thrombolytic therapy. Typically,thrombolytic therapy may take up to 1-2 hours or more to clear ablockage after the bolus has been delivered. Mechanical thrombectomy mayalso take up to 1 to 2 hours to successfully recanalize the blockedartery. Distal perfusion of the ischemic region may minimize the levelof brain injury during the stroke treatment procedure. Embodiments ofdistal perfusion means are described below.

FIG. 31 shows a perfusion catheter 3600 positioned across the thromboticblockage 10, to enable perfusion distal to the blockage. In anembodiment, the catheter is 3600 positioned over a guidewire placedthrough a lumen in the catheter. The lumen may serve as both a guidewirelumen and a perfusion lumen. Once placed, the guidewire may be removedto maximize the throughspace of the lumen available for perfusion.Alternately, the guidewire lumen and the perfusion lumen may be twoseparate lumens within the catheter, so that the guidewire may remain inplace in the guidewire lumen during perfusion without interfering withthe perfusion lumen. Perfusion exit holes 3615, which communicate withthe perfusion lumen, are located in a distal region of the catheter3600. This perfusion lumen may be connected to a perfusion source suchas a perfusion pump or syringe and may be used for perfusing fluid suchas neuroprotective agents and/or oxygenated blood such as the patient'sown arterial blood via the perfusion exit holes 3615 as exhibited by thearrows P in FIG. 32, which represent the flow of perfusion solution outof the catheter 3600. Alternately, the catheter 3600 may be positionedrelative to the blockage 10 such that the perfusion exit holes 3615 areinitially positioned just proximal to, or within, the thromboticblockage 10 during a bolus of thrombolytic infusion. The catheter canthen be re-positioned so that at least some of the perfusion exit holes3615 are located distal of the blockage 10 to provide distal perfusionwith blood or an equivalent solution to the ischemic penumbra. Theperfusion catheter may be used in conjunction with mechanical oraspiration thrombectomy as above. The catheter may be positioned throughthe lumen of access device 2010 or distal catheter 2030. The cathetermay be placed side by side with mechanical thrombectomy means in thelumen, or may be co-axial with mechanical thrombectomy device.

FIG. 32 shows another embodiment of a perfusion catheter 3600 with aperfusion lumen 3610 that communicates with side holes 3615 and/or anend opening 3616 for perfusing fluid, and a second lumen 3612 forpressure monitoring. The pressure monitoring lumen 3612 is closed off ata distal-most end 3613. A side opening 3614 to the lumen 3612 is locatedproximal of the distal-most end 3613 for measuring perfusion pressure.The catheter 3600 is shown without an expandable occlusion elementalthough it could include an expandable occlusion element such as anocclusion balloon. The occlusion element may be positioned either distalto or proximal to the side holes 3615. In an embodiment, the perfusionsource may be controlled by the perfusion pressure measurement tomaintain perfusion pressure below 200 mm Hg. In an embodiment, theperfusion flow rate is controlled to maintain perfusion in the range ofabout 50 ml/min to about 250 ml/min.

In an alternate embodiment, as shown in FIG. 33, distal perfusioncatheter 3700 includes an occlusion balloon 3705, with perfusion exitholes 3715 positioned distal to, and/or proximal to the occlusionballoon 3705. As with the previous embodiment, the perfusion catheter3700 may be used in conjunction with recanalization therapies such asthrombectomy devices, aspiration means or intra-arterial thrombolyticinfusion. The catheter 3700 is placed in the vasculature so that theocclusion balloon 3705 is positioned distal to the blockage 10. Thecatheter 3700 may be configured to perfuse the region distal of theballoon 3705 with blood or equivalent, and the region proximal of theballoon 3705 with thrombolytic agents. In this regard, the catheter 3700may include separate perfusion lumens 3720 and 3725 that communicatewith separate perfusion exit holes, as shown in FIG. 34. Alternately, asshown in FIG. 35, the distal and proximal perfusion exit holes areconnected to the same perfusion lumen 3630, and regions both distal andproximal to the occlusion balloon are used to infuse blood or alternateperfusion solution. Not shown in either FIG. 34 or 35 is a separatelumen for inflation and deflation of occlusion balloon 3705. This lumenmay be embedded into the wall of the catheter.

In another embodiment, as shown in FIG. 36, the expandable occlusiondevice 3705 is a dilatation balloon which may provide a dilatation forceon the thrombus while the catheter 3700 is perfusing the distalvasculature.

The perfusion catheter may also provide perfusion to aid in thrombusremoval. FIG. 37 shows a proximal perfusion catheter 3800 being deployeddistal of the occlusion via the arterial access device 2010. Theproximal perfusion catheter 3800 includes an expandable occlusionelement 3829 such as an occlusion balloon. The proximal perfusioncatheter 3800 also includes one or more perfusion exit holes 3820 at alocation proximal to the occlusion element 3829. The perfusion exitholes 3820 communicate with an internal perfusion lumen in the perfusioncatheter 3800 for perfusion of fluid out through the perfusion exitholes 3820. With reference still to FIG. 37, the proximal perfusioncatheter 3800 is deployed into the vasculature via the arterial accessdevice so that the occlusion element 3829 of the perfusion catheter ispositioned and expanded distal to the thrombus 10 with the perfusionexit holes 3820 positioned proximal to the occlusion element 3829 anddistal to the thrombus 10. Such an arrangement provides back pressure toassist in removal of the thrombus 10. In addition, the occlusion element3829 serves as distal emboli protection. Any of a variety of perfusionfluids may be used including, for example, oxygenated blood,neuroprotection agents, thrombolytics, as well as other fluids, whichmay be adjusted to a desired temperature. The arterial access device2010 can be used for aspiration in the arrangement of FIG. 37. Thearterial access device 2010 may have occlusion balloon 2020 as well aspassive or active aspiration means. The perfusion catheter facilitatesremoval of the thrombus into the arterial access device 2010 and thencethrough the flow line 2025 and out of the patient.

Alternately, as shown in FIG. 38, the proximal perfusion catheter 3800may be delivered via distal catheter 2030. When aspiration is initiatedthrough the distal catheter 2030 and perfusion is initiated throughproximal perfusion catheter 3800 there is a pressure gradient in aretrograde direction which aids in removal of thrombus 10 from thevessel, and into the lumen of distal catheter 2030. The arterial accessdevice 2010 and distal catheter 2030 may simultaneously aspirate. Or,the aspiration may be applied sequentially between the arterial accessdevice 2010 and the distal catheter 2030. For example, the distalcatheter 2030, when positioned as shown in FIG. 38, can aspirate. Thedistal catheter 2030 can then be withdrawn into the arterial accessdevice 2010 and the aspiration applied from the arterial access device.

In addition to providing pressure distal to the occlusion, the perfusionfluid from proximal perfusion catheter 3800 can supply blood to smallervessels (perforators) originating in or just proximal to the occlusion.The shaft of the perfusion catheter 3800 may also be used as a rail orconduit for delivery of a therapeutic device such as stentriever orthrombectomy device.

In an embodiment, the perfusion lumen and the guide wire lumen are twoseparate lumens, configured for example as in FIG. 32. In an alternateembodiment, the perfusion lumen of the perfusion catheter 3800 alsoserves as a guide wire lumen. In such an arrangement, a valve isdesirably located at the distal end opening of the perfusion/guide wirelumen. When the guide wire is pushed distally out of the distal endopening of the guide wire lumen, the guide wire opens the valve. Thevalve automatically closes when the guide wire is retracted proximallyback into the lumen. In this manner, the valve seals the distal endopening of the lumen after the guide wire is retracted. The valve canalso be a pressure relief valve such that if the perfusion pressure istoo high, the valve opens to release the pressure.

FIGS. 39A-39D show an exemplary method of use of proximal perfusioncatheter 3800. FIG. 39A shows an enlarged view of a guide wire 3912positioned across the thrombus 10 in a cerebral artery. In FIG. 39B, adistal region of the perfusion catheter 3800 has been positioned acrossthe thrombus 10 (via the guide wire 3912) with the unexpanded occlusionelement 3829 positioned distal of the thrombus 10. The guide wire 3912protrudes out of the distal end of the guide wire lumen of the perfusioncatheter 3800. In FIG. 39C, the guide wire is not shown as it has beenretracted back into the guide wire lumen of the perfusion catheter 3800.If the guide wire lumen also serves as a perfusion lumen for theperfusion catheter 3800, a distal valve 3916 (such as a duckbill valve)at the distal end of the guide wire/perfusion lumen has automaticallyclosed such that the lumen can now be used for perfusion via theperfusion exit holes 3820, as represented by the arrows P in FIG. 34C.When the occlusion element 3829 is unexpanded (as shown in FIG. 39C),the perfusion exit holes 3820 can be used to perfuse distally. In FIG.39D, the expandable occlusion element 3829 has been expanded in theartery. The perfusion exit holes 3820 can then be used for perfusionproximal of the occlusion element 3829, as represented by the arrows P1in FIG. 39D.

Perfusion catheters 3600 or 3800 may include an element for monitoringblood pressure. In an embodiment, the pressure monitoring element is adedicated internal lumen in the perfusion catheter 3600 or 3800, whereinthe lumen is fluid-filled and connected to a pressure transducer on theproximal end of the perfusion catheter. A pressure transducer on thecatheter itself may also be used. Alternately, a pressure measuringguide wire may be inserted through an internal lumen of the perfusioncatheter 3600 or 3800 to a location where pressure is to be monitored.

An alternate means for cerebral perfusion comprises cerebralretroperfusion as described by Frazee et al. This embodiment involvesselective cannulation and occlusion of the transverse sinuses via theinternal jugular vein, and infusion of blood via the superior sagittalsinus to the brain tissue, during treatment of ischemic stroke. Thefollowing articles, which are incorporated herein by reference in theirentirety, described cerebral retroperfusion and are incorporated byreference in their entirety: Frazee, J. G. and X. Luo (1999).“Retrograde transvenous perfusion.” Crit Care Clin 15(4): 777-88, vii.;and Frazee, J. G., X. Luo, et al. (1998). “Retrograde transvenousneuroperfusion: a back door treatment for stroke.” Stroke 29(9): 1912-6.This perfusion, in addition to providing protection to the cerebraltissue, may also cause a retrograde flow gradient in the cerebralarteries. Used in conjunction with the system 100, a retroperfusioncomponent may provide oxygen to brain tissue, as well as aid in captureof embolic debris into the reverse flow line during recanalization ofthe thrombotic occlusion 10.

It should be appreciated that other perfusion catheters or systems maybe used with the system 100, for example those described by U.S. Pat.Nos. 6,435,189 and 6,295,990, which are incorporated by reference intheir entirety.

Exemplary Methods and Devices for Transcervical Vessel Closure

Any type of closing element, including a self-closing element, asuture-based closing element, or a hydrostatic seal element, may bedeployed on or about the penetration in the wall of the common carotidartery prior to withdrawing the arterial access device 2010 orintroducer sheath 2110 (the procedural sheath) at the end of theprocedure. The following U.S. Patent Applications, which areincorporated herein by reference in their entirety, describe exemplaryclosure devices and methods: U.S. Patent Publication No. 20100042118,entitled “Suture Delivery Device”, and U.S. Patent Publication No.20100228269, entitled “Vessel Closure Clip Device”.

The closing element may be deployed at or near the beginning of theprocedure in a step termed “pre-closure”, or, the closing element couldbe deployed as the sheath is being withdrawn. In an embodiment, themeans for vessel closure is a suture-based blood vessel closure device.The suture-based vessel closure device can place one or more suturesacross a vessel access site such that, when the suture ends are tied offafter sheath removal, the stitch or stitches provide hemostasis to theaccess site. The sutures can be applied either prior to insertion of theprocedural sheath through the arteriotomy or after removal of the sheathfrom the arteriotomy. The device can maintain temporary hemostasis ofthe arteriotomy after placement of sutures but before and duringplacement of a procedural sheath, if a pre-closure step us used, and canalso maintain temporary hemostasis after withdrawal of the proceduralsheath but before tying off the suture. Some exemplary suture-basedblood vessel disclosure devices are described in the following U.S.Patents, which are incorporated herein by reference in their entirety:U.S. Pat. Nos. 6,562,052; 7,001,400; and 7,004,952.

In an embodiment, the system includes an ultrasound probe element, whichwhen used with an ultrasound imaging system is configured to identifythe desired site of carotid arterial access to determine that issuitable for percutaneous puncture, for example to verify that there isno vascular disease in the vessel. The probe will also visualizesurrounding anatomy such as the internal jugular vein, to ensure thataccess can be achieved without comprising these other structures. Inaddition, the probe may be used to visualize the access site aftervessel closure to verify that hemostasis has been achieved. If needed,the probe may be used to provide localized compression at the site ofthe puncture as needed to ensure hemostasis. For example, after vesselclosure the probe is used to image the closure site. If blood is seenflowing from the site, the probe is pressed down to compress the site.The user periodically relaxes the pressure on the probe to assess ifhemostasis has been achieved. If it has not, pressure is reapplied. Ifit has, the probe may be removed.

Exemplary Methods of Use

As illustrated in FIG. 1, the arterial access device 2010 istranscervically introduced directly into the common carotid artery CCAof the patient. This may be done with a percutaneous puncture or adirect cut-down. In the case of a puncture, ultrasound imaging may beused to accurately make the initial arterial puncture. The arterialaccess device 2010 is threaded through the vasculature such that thedistal tip is positioned in the common carotid artery or the proximal ordistal cervical, petrous, or cavernous portion of the internal carotidartery ICA. A removable proximal extension may be used to place thearterial access device 2010 under fluoroscopy without exposing theuser's hand to radiation. U.S. patent application Ser. No. 12/834,869,filed Jul. 12, 2010, describes exemplary embodiments of removableproximal extensions and is incorporated herein by reference.

Once the arterial access device is positioned, a diagnostic angiogrammay be performed via a microcatheter placed through the arterial accessdevice. The microcatheter may be for angiographic injections bothproximal and distal to the occlusion. Diagnostic angiograms areperformed throughout the procedure to determine the progress in removingthe occlusion or occlusions.

If the arterial aspiration device has an occlusion balloon, the balloonmay be inflated at this time and aspiration may be applied to thearterial access device. Because the tip of the aspiration device is somedistance proximal to the occlusion, the aspiration force is not directlyapplied to the occlusion. However, in some cases, this proximalaspiration may service to remove some or all of the occlusion. Onceaspiration from the access device is finished, the occlusion balloon maybe deflated so that antegrade flow may resume in the artery.

A distal catheter 2030 is placed through the arterial access device andpositioned such that the distal tip reaches the site of the occlusion.If desired, a coaxial system of devices comprising a guide wire, amicrocatheter, and the distal catheter 2030 are inserted togetherthrough the arterial access device 2010 and advanced towards thecerebral occlusion. Alternately, a tapered dilator with or without amicrocatheter tip may be substituted for the microcatheter. Alternately,a microcatheter and guide wire may be placed inside the tapered dilator.The removable proximal extension, if used, may be removed prior tointroduction of the telescoping devices, or the devices may be insertedthrough the removable proximal extension. The microcatheter, or tapereddilator, and guide wire are then advanced to access and cross thecerebral occlusion. The microcatheter or dilator may be used to performthe angiogram of the cerebral circulation proximal and distal to theocclusion. The microcatheter may also used as a rail to advance thedistal catheter.

Typically, the largest size distal catheter will be selected which isable to be safely navigated to the occlusion, to maximize the force andluminal area for aspiration of the occlusion. Aspiration is theninitiated through the distal catheter, This may be done manually, withan aspiration pump or other aspiratin source, or via the flow controlleras described above. If the thrombus is too large or too stronglyembedded into the vasculature such that it is not possible to remove theocclusion via aspiration alone, further steps are taken to remove theocclusion. A thrombectomy device may be deployed through the arterialaccess device to remove the clot. During clot retrieval, passive oractive aspiration may be applied via the arterial access device tominimize or eliminate the amount of distal emboli.

If the distal catheter is unable to reach the occlusion, or if asecondary more distal occlusion needs to be reached after removal of afirst occlusion, a second, smaller diameter distal catheter may beinserted through the first distal catheter, and positioned at the siteof the occlusion. Alternately, the first distal catheter may be removedand exchanged for the second distal catheter. A guidewire and/ormicrocatheter may be placed through the first distal catheter tofacilitate the exchange. Once at the target site, aspiration may beinitiated through the second catheter as above, or additional devicesmay be inserted to aid in removal of the occlusion.

If there is difficulty navigating the distal catheter of the desiredsize to a location just proximal to the clot, a device may be deployeddistal to the clot and expanded to act as an anchor to aid in advancingthe distal catheter as shown in FIG. 6 or 7. If desirable, a seconddistal catheter may be used in a telescoping manner to create supportfor the first distal catheter to access the proximal face of theocclusion. Alternately, a tapered dilator as shown in FIG. 8 may be usedin addition to or in place of the microcatheter to facilitate navigationof the distal catheter. The arterial access device 2010 and the distalcatheter 2030 may be connected to means for passive or activeaspiration, as shown in FIGS. 15-17, or a flow controller 3400 as shownin FIG. 18. In one embodiment, the arterial access device 2010 isconnected to passive aspiration and the distal catheter 2030 isconnected to active aspiration. In another embodiment, both devices areconnected to active aspiration. During the procedure, the user may openor close the connections to the passive and/or active aspiration sourcesas desired. For example, when the distal catheter 2030 is positioned atthe proximal face of the clot, the active aspiration may be initiated toapply suction to the occlusion with the goal to remove the occlusion. Ifa locking syringe was used and an additional aspiration step is desired,the syringe may be removed, emptied, reattached and re-locked foradditional aspiration.

In another embodiment, the microcatheter is used to deliver athrombectomy device such as a coil or stentriever in or beyond theocclusion. The device is then pulled towards the distal catheter toremove the occlusion, aided by aspiration of the distal catheter. Theocclusion is then pulled back using the distal catheter, thrombectomydevice, and/or microcatheter into the arterial access device. In yetanother embodiment, the microcatheter has two lumens as shown in FIGS.11 and 12, such that the guide wire may be left across the occlusionwhen the microcatheter and/or thrombectomy device are pulled proximallyto remove the occlusion.

At any time during the procedure, the balloon on the arterial accessdevice may be inflated at this point to reduce forward arterial pressureon the occlusion. The inflated balloon may also increase the stabilityof the arterial access in the vessel to increase the support foradvancement of devices through the arterial access device. Additionally,the arterial access device may be connected to passive or activeaspiration as desired to provide embolic protection while notcompromising collateral flow to the ischemic penumbra of the patient.This may be accomplished by selective periods of reverse, stopped, andantegrade flow, for example reverse flow initiated during periods whenthe occlusion is being pulled towards and/or entering the guidecatheter. Multiple devices or sizes of devices may be used as needed toremove the occlusion or occlusions. At the conclusion of the procedure,the arterial access catheter may be exchanged for a shorter introducersheath and a vessel closure device may be used to achieve hemostasis atthe access site. Ultrasound may again be employed, in this instance toascertain and/or ensure hemostasis. If appropriate, the ultrasound probemay be used to apply pressure at the access site until hemostasis isachieved.

In a variation of this procedure, the arterial access device is insertedthrough an introducer sheath which has been previously inserted into theCCA. An example of this configuration is shown in FIG. 2. In thisscenario, the arterial access device may be removed and cleared onto atable during the procedure in case the device becomes blocked andaspiration is slowed or stopped, or may be exchanged for another size ortype of catheter as needed without loss of arterial access. In addition,there is no need to exchange the sheath at the conclusion of theprocedure before utilizing a vessel closure device. The introducersheath may incorporate a removable proximal extension such that duringthe procedure there is limited exposure of radiation to the users'hands. If used, the proximal extension may be removed prior to closureof the access site with a vessel closure device.

In yet another embodiment, the system may be used to deliverintra-arterial thrombolytic therapy, such as through a sidearm in thearterial access device 2010. For example, thrombolytic therapy may beinfused to the thrombotic occlusion 10 through the arterial accessdevice 2010, or through the distal catheter 2030. In another embodiment,the system may be used to deliver intra-arterial thrombolytic therapyvia a micro catheter which is inserted into the arterial access device2010. The micro catheter is delivered to the site of the thromboticocclusion 10 to infuse a thrombolytic drug. The thrombolytic therapy maybe delivered either in conjunction with or as an alternative tomechanical thrombectomy or aspiration.

In yet a further embodiment, the system is used to provide distalprotection and/or perfusion during the procedure. In this embodiment, aperfusion catheter is inserted through the arterial access device 2010or through the distal catheter 2030, and positioned across the lumen andinflated at a point distal to the occlusion. The perfusion catheter maybe connected to a perfusion pump to perfuse oxygenated blood orperfusion solution to the ischemic brain via a distal opening in theperfusion catheter. In an embodiment, the perfusion catheter is aballoon-tipped catheter. The balloon is inflated at a point distal tothe occlusion. This balloon acts to prevent emboli from progressingdistally during removal or recanalization of the occlusion. Theperfusion catheter may also be connected to a flush source to perfuseproximal to the occlusion balloon via proximal ports in the perfusioncatheter. This maneuver essentially provides a back pressure on theocclusion and may aid it its removal.

In the instance where there is also a carotid artery stenosis whichrequires treatment either before or after treatment of the cerebralocclusion, an angioplasty balloon or stent may be deployed in thestenosis via the introducer sheath. If embolic protection is desirableduring intervention of the carotid stenosis, the introducer sheath mayhave an occlusion balloon and a connection to a reverse flow line asshown in FIG. 3, and the CAS procedure may be conducted under reverseflow embolic protection as described in co-pending U.S. patentapplication Ser. No. 12/176,250, which is incorporated herein byreference. The introducer sheath is then used to place the arterialaccess device into the ICA. Alternately, the introducer sheath may havetwo occlusion balloons as shown in FIG. 4, with an opening to allowballoon angioplasty or stenting of the carotid stenosis, and subsequentintroduction of devices such as a distal catheter into the ICA andcerebral circulation for treatment of the cerebral occlusion.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of an invention that is claimed orof what may be claimed, but rather as descriptions of features specificto particular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults.

Although embodiments of various methods and devices are described hereinin detail with reference to certain versions, it should be appreciatedthat other versions, embodiments, methods of use, and combinationsthereof are also possible. Therefore the spirit and scope of theappended claims should not be limited to the description of theembodiments contained herein.

The invention claimed is:
 1. A system of devices for treating anocclusion in a cerebral artery of a patient, comprising: a transcervicalaccess sheath adapted to be introduced into a common carotid artery viaan opening directly in the artery, the opening being positioned abovethe patient's clavicle and below a bifurcation location where thepatient's common carotid artery bifurcates into an internal carotidartery and external carotid artery, wherein the transcervical accesssheath has an internal lumen and a portion that splits into a first,proximal, expandable region and a second proximal, expandable region inparallel to the first proximal, expandable region; a distal cathetersized and shaped to be inserted axially through the internal lumen ofthe transcervical access sheath such that the distal catheter can beinserted into a cerebral artery via the transcervical access sheath,wherein the distal catheter has an internal lumen defined by an innerdiameter, and wherein the distal catheter is longer than the accesssheath and wherein the distal catheter has a length sufficient for adistal end of the distal catheter to reach a cerebral artery when aproximal region of the distal catheter is located in the common carotidartery, and wherein a distal region of the distal catheter is moreflexible than a proximal region of the distal catheter, and wherein thedistal catheter has a total length such that a proximal-most region ofthe distal catheter can be positioned in the common carotid artery whilethe distal region of the distal catheter is simultaneously positioned inthe cerebral artery; an elongated inner member sized and shaped to beinserted axially through the lumen of the transcervical access sheath,wherein the inner member has an internal lumen; a guidewire configuredto be inserted into the cerebral artery via internal lumen of the innermember; wherein the inner member has an outer diameter configured toform a smooth transition between the inner diameter of the distalcatheter and the outer diameter of the guidewire; and a first aspirationpump device fluidly connected to the internal lumen of the accesssheath, the pump device including a first outer housing that encloses afirst chamber that contains the first proximal, expandable region of theaccess sheath; a second aspiration pump device fluidly connected to theinternal lumen of the access sheath, the pump device including a secondouter housing that encloses a second chamber that contains the secondproximal, expandable region of the access sheath, wherein the firstaspiration pump device and the second aspiration pump device alternatebetween expanded and retracted states such that the first aspirationpump device is in in an expanded state while the second aspiration pumpdevice is in in a retracted state such that the first aspiration pumpdevice and the second aspiration pump device collectively drive fluidthrough the internal lumen of the access sheath; a vacuum source coupledto the chamber of the aspiration pump device, wherein the vacuum sourceactivates to create a reduced pressure within the chamber relative tothe pressure within the internal lumen of the access sheath to cause theproximal, expandable region of the access sheath to expand to anincreased volume within the chamber and thereby pull blood into theproximal, expandable region of the access sheath; a first check valve atan entranceway to the chamber of the aspiration pump device, wherein thefirst check valve is a one-way check valve that opens to permit fluid toflow only in a direction into the chamber when the proximal, expandableregion of the access sheath expands to an increased volume within thechamber; and a second check valve at an exit way out of the chamber ofthe aspiration pump device, wherein the second check valve is a one-waycheck valve that opens to permit fluid to flow only in a direction outof the chamber.
 2. The system of claim 1, wherein a distal, taperedregion of the inner member has an outer diameter that tapers in sizetoward the outer diameter of the guidewire.
 3. The system of claim 1,wherein the inner member has a first, tapered region having an outerdiameter that tapers toward the outer diameter of the guidewire, and asecond distal-most region having an outer diameter that is constant, andwherein the guidewire protrudes out of the distal-most region.
 4. Thesystem of claim 1, further comprising a flow line connected to theaccess sheath, wherein the flow line provides a pathway for blood toflow from the access sheath to a return site.
 5. The system of claim 4,further comprising a flow controller coupled to the transcervical accesssheath and adapted to regulate blood flow through the transcervicalaccess sheath.
 6. A system of devices as in claim 1, further comprisinga radio-opaque marker at a distal end of the distal catheter.
 7. Asystem of devices as in claim 1, wherein the distal region of the distalcatheter is 3 cm to 6 cm in length.
 8. A system of devices as in claim1, wherein the distal catheter has a plurality of sections, and whereinthe sections increase in stiffness moving in a proximal direction alongthe distal catheter.
 9. A system of devices as in claim 1, wherein thedistal catheter has a length longer than a length of the transcervicalaccess sheath such that a proximal end of the distal catheter canprotrude from a proximal end of the transcervical access sheath and adistal end of the distal catheter can protrude from the distal openingof the transcervical access sheath when the distal catheter ispositioned inside the transcervical access sheath.
 10. A system ofdevices as in claim 9, wherein the distal end of the distal catheter canprotrude from the distal opening of the transcervical access sheath by15-25 cm.
 11. A system of devices as in claim 1, wherein the distalcatheter has a working length of 40 to 80 cm.
 12. A system of devices asin claim 11, wherein the transcervical access sheath has a workinglength of 10 to 15 cm.
 13. A system of devices as in claim 11, whereinthe transcervical access sheath has a working length of 15 to 25 cm. 14.A system of devices as in claim 1, wherein the distal catheter is alsoconnected to the vacuum source.